Changes in the muscle growth and regulatory factors, TNF-α and Toll-like Receptors 2 and 4 during Exercise, Muscle Atrophy, and Recovery in the Mouse Hind Limb Suspension Model

Abstract Background Muscle atrophy, characterized by muscle weakening and a reduction in mass, is primarily caused by inactivity or injury. The molecular mechanisms that drive skeletal muscle growth and development remain poorly understood, hampering the development of novel techniques for treating or preventing muscle atrophy. This study aimed to assess changes in muscle growth and the level of regulatory factors, including TNF-α and Toll-like Receptors 2 and 4, during Exercise, Muscle Atrophy, and Recovery in a Mouse Hind Limb Suspension Model. Methodology Adult male mice were subjected to hind limb unloading to induce muscle wasting for one week. Eighty animals were divided into four main groups: weight-bearing control (Con) group, Hindlimb unloading (HU) group, Hindlimb unloading + exercise training (HU + Ex) group, and exercise training (Exe) group. Total RNA was extracted from the Gastrocnemius muscle, and selected gene expression was evaluated using RT-qPCR analysis. Results Distinct gene expression patterns were observed in response to hindlimb unloading (HU) and hindlimb unloading with exercise (HU + Ex). There was a significant decrease in TLR-2 expression in the HU group, while TLR-4 levels increased compared to those in the other groups. TNF-α expression increased substantially in almost all groups except for the control group. IGF-1 increased with exercise and decreased during HU, showing recovery in the HU + Ex group. Markers of muscle atrophy, MyoG, and MyoD increased during HU and dropped in HU + Ex. Myostatin, MurF, and Atrogin were linked to atrophy, which increased in both the exercised and recovered groups. Exercise increased Irisin expression compared to controls, while HU and HU + Ex groups showed decreased levels but were still elevated compared to controls. Conclusion Understanding the changes in muscle growth and regulatory factors, TNF-α and Toll-like Receptors 2 and 4 during exercise, muscle atrophy, and recovery in the mouse hind limb suspension model can add significant value to the existing data on molecular and cellular mechanisms during and post hind limb recovery from muscle atrophy (hind limb suspension).